Luteinizing hormone response to gonadotrophin-releasing hormone in normal women undergoing ovulation induction with urinary or recombinant follicle stimulating hormone

Oestradiol enhances pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) in normal women, while in women undergoing ovulation induction the putative factor gonadotrophin surge attenuating factor (GnSAF) attenuates the response of luteinizing hormone (LH) to GnRH. To study the relationships between oestradiol and GnSAF during ovulation induction, 15 normally ovulating women were investigated in an untreated spontaneous cycle (control, first cycle), in a cycle treated with daily i.m. injections of 225 IU urinary follicle-stimulating hormone (FSH) (Metrodin HP, uFSH cycle) and in a cycle treated with daily s.c. injections of 225 IU recombinant FSH (Gonal-F, rFSH cycle). Treatment with FSH started on cycle day 2. The women during the second and third cycle were allocated to the two treatments in an alternate way. One woman who became pregnant during the first treatment cycle (rFSH) was excluded from the study. In all cycles, an i.v. injection of 10 microg GnRH was given to the women (n = 14) daily from days 2-7 as well as from the day on which the leading follicle was 14 mm in diameter (day V) until mid-cycle (n = 7). The response of LH to GnRH at 30 min (deltaLH), representing pituitary sensitivity, was calculated. In the spontaneous (control) cycles, deltaLH values increased significantly only during the late follicular phase, i.e. from day V to mid-cycle, at which time they were correlated significantly with serum oestradiol values (r = 0.554, P < 0.01). Initially during the early follicular phase in the uFSH and the rFSH cycles, deltaLH values showed a significant decline which was not related to oestradiol (increased GnSAF bioactivity). Then, deltaLH values increased significantly on cycle day 7 and further on day v with no change thereafter up to mid- cycle. On these two days, deltaLH values were correlated significantly with serum oestradiol values (r = 0.587 and r = 0.652 respectively, P < 0.05). During the pre-ovulatory period, deltaLH values in the FSH cycles were significantly lower than in the spontaneous cycles. Significantly higher serum FSH values were achieved during treatment with uFSH than rFSH. However, serum values of oestradiol, immunoreactive inhibin, and deltaLH as well as the number of follicles > or = 12 mm in diameter did not differ significantly between the two FSH preparations. These results suggest that in women undergoing ovulation induction with FSH, oestradiol enhances pituitary sensitivity to GnRH, while GnSAF exerts antagonistic effects. The rFSH used in this study (Gonal-F) was at least as effective as the uFSH preparation (Metrodin-HP) in inducing multiple follicular maturation in normally cycling women.      

Pericardial complications of peptic ulceration

Intrathoracic perforated peptic ulceration is uncommon. Two patients are reported with pericardial fistulization secondary to peptic ulceration. These occurred following colonic bypass surgery as a consequence of peptic esophagitis and hiatus hernia.     

Functional differences between two Fc receptor ITAM signaling motifs

Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand- binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.     

Large paraesophageal varices on endosonography predict recurrence of esophageal varices and rebleeding

BACKGROUND & AIMS: Recurrence of varices and rebleeding after endoscopic therapy is very common. Data on the prediction of recurrent varices after initial obliteration by endoscopic therapy are few. The aim of this study was to correlate the presence and the size of paraesophageal varices (PEVs) in patients after endoscopic variceal ligation with recurrent varices and rebleeding. METHODS: Forty patients who underwent endoscopic banding ligation for esophageal variceal bleeding were studied by endosonography within 4 weeks after obliteration of varices. PEVs were classified as none, small, or large (maximum diameter, > or =0.5 cm). Esophagoscopy and endosonography were then repeated every 6 months for up to 1 year. RESULTS: Two patients (5%) were not detected to have PEVs. Small and large PEVs were identified in 24 (60%) and 14 (35%) patients, respectively. During the follow-up period of 1-year, recurrent submucosal esophageal varices were detected in 24 patients, including 13 patients (93%) with large PEVs and 11 patients (46%) with no or small PEVs (P = 0.0019). Recurrent bleeding occurred in 6 patients (43%) with large PEVs and in 3 patients (12%) with small PEVs (P = 0.044). CONCLUSIONS: Patients with large PEVs have a higher risk of developing recurrent varices and rebleeding. (Gastroenterology 1997 Jun;112(6):1811-6)     

Essential requirement of an invariant V alpha 14 T cell antigen receptor expression in the development of natural killer T cells.

NK1.1+ T [natural killer (NK) T] cells express an invariant T cell antigen receptor alpha chain (TCR alpha) encoded by V alpha 14 and J alpha 281 segments in association with a limited number of V betas, predominantly V beta 8.2. Expression of the invariant V alpha 14/J alpha 281, but not V alpha 1, TCR in transgenic mice lacking endogenous TCR alpha expression blocks the development of conventional T alpha beta cells and leads to the preferential development of V alpha 14 NK T cells, suggesting a prerequisite role of invariant V alpha 14 TCR in NK T cell development. In V beta 8.2 but not B beta 3 transgenic mice, two NK T cells with different CD3 epsilon expressions, CD3 epsilon(dim) and CD3 epsilon(high), can be identified. CD3 epsilon(high) NK T cells express surface V alpha 14/V beta 8 TCR, indicating a mature cell type, whereas CD3 epsilon(dim) NK T cells express V beta 8 without V alpha 14 TCR and no significant CD3 epsilon expression (CD3 epsilon(dim)) on the cell surface. However, the latter are positive for recombination activating gene (RAG-1 and RAG-2) mRNA, which are only expressed in the precursor or immature T cell lineage, and also possess CD3 epsilon mRNA in their cytoplasm, suggesting that CD3 epsilon(dim) NK T cells are the precursor of V alpha 14 NK T cells.     

Sex-related differences in disposition and response to phenprocoumon in rats

The pharmacokinetics and the pharmacological response to phenprocoumon have been studied in female and male inbred Lewis-Wistar rats. A significantly lower clearance was found in female than in male rats (7.9 +/- 1.4 vs 24.5 +/- 2.5 mL h-1 kg-1, respectively; t = 15.09, P less than 0.001) as well as a lower apparent volume of distribution (288 +/- 46 vs 617 +/- 105 mL kg-1; t = 7.58, P less than 0.001) and a longer half-life (25.5 +/- 3.4 vs 17.5 +/- 1.8 h; t = 5.16, P less than 0.001). The binding of phenprocoumon was higher in female than in male rats (fu: 0.0096 +/ 0.0008 vs 0.0124 +/- 0.0007, respectively; t = 6.66, P less than 0.001). The total (C) as well as the unbound concentration (Cu) needed to elicit a 50% decrease in the prothrombin complex synthesis rate was substantially higher in female rats: C50 was 377 +/- 98 ng mL-1 in female and 155 +/- 29 ng mL-1 in male rats (t = 5.32, P less than 0.001), whereas Cu50 was 3.6 +/- 0.7 ng mL-1 in female and 1.9 +/- 0.3 ng mL-1 in male rats (t = 5.50, P less than 0.001). However, because of the lower clearance and volume of distribution and the longer half-life in female rats, the female rats experienced a higher cumulative effect than male rats to 0.34 mg kg-1 i.v. doses.     

In vitro function and post-transfusion survival of granulocytes collected by continuous-flow centrifugation and by filtration leukapheresis

The function of granulocytes collected by continuous-flow centrifugation (CFC) and by filtration leukapheresis (FL) was studied in vitro, and the post-transfusion recovery and intravascular survival of these cells was studied by autologous transfusion in normal donors. Granulocytes collected by both FL and CFC leukapheresis (CFCL) functioned normally in the quantitative nitroblue tetrazolium, oxygen consumption, and chemotaxis assays. Bacterial killing was slightly but consistently decreased in FL but not CFCL granulocytes. The post- transfusion recovery of control granulocytes collected by ordinary phlebotomy averaged 52% in eight transfusions, compared with 34% for six CFCL granulocyte concentrates and 16% for six FL concentrates. The intravascular half-times were 3.8 hr for phlebotomy and 3.0 hr for CFCL granulocytes. FL granulocytes had survival curves which were nonlinear and a single half-life could not be calculated. The average half-time 30 min after transfusion was 1.3 hr, and 3 hr after transfusion it was 2.6 hr. Granulocytes collected by FL had a mild impairment of bacterial killing, decreased post-transfusion recovery, and altered intravascular kinetics. None of these abnormalities was found in granulocytes collected by CFCL.